Mutations

PSEN1 V261I

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37 (105)
Position: Chr14:73664750 G>A
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: GTT to ATT
Reference Isoform: PSEN1 isoform 1 (467 aa)
Genomic Region: Exon 8

Findings

This mutation was found in an individual diagnosed with familial AD (Miravalle et al., 2005). Symptoms emerged at age 48 and death occurred at 55. The patient was homozygous for the APOE3 allele and had no mutations in exons 16 and 17 of the APP gene. Although the disease was described as familial, no information was reported for family members.

Neuropathology
Neuropathology was consistent with AD, including neuritic plaques, diffuse amyloid deposits, and cotton wool plaques. The latter were the most abundant amyloid species, with widespread distribution in the neocortex, caudate nucleus, putamen, thalamus, amygdala, hippocampus, parahippocampus, and midbrain. The predominant Aβ species in cotton wool plaques were amino-terminally truncated Aβ42 and Aβ43 peptides, with no detectable Aβ40. A similar Aβ composition was observed in the diffuse amyloid deposits of the cerebellum. In contrast, in the amyloid deposits associated with parenchymal and leptomeningeal vessels, Aβ40 was the predominant species.

Biological Effect
Unknown.

Last Updated: 23 Aug 2019

Comments

  1. This interesting paper corroborates the new concept that N-terminal truncated Aβ42 species are the seeds of amyloidosis, and a nice target for the vaccination approach.

    References:

    . Truncated beta-amyloid peptide species in pre-clinical Alzheimer's disease as new targets for the vaccination approach. J Neurochem. 2003 Jun;85(6):1581-91. PubMed.

    View all comments by Andre Delacourte

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References

Paper Citations

  1. . Amino-terminally truncated Abeta peptide species are the main component of cotton wool plaques. Biochemistry. 2005 Aug 16;44(32):10810-21. PubMed.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . Amino-terminally truncated Abeta peptide species are the main component of cotton wool plaques. Biochemistry. 2005 Aug 16;44(32):10810-21. PubMed.

Other mutations at this position

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